Burnett School of Biomedical Sciences, College of Medicine, University of Central Florida, Orlando, FL 32827, USA.
Faculdade de Medicina, Universidade de Fortaleza, Fortaleza 60811-905, CE, Brazil.
Aging (Albany NY). 2020 Jan 18;12(3):2711-2722. doi: 10.18632/aging.102772.
The uterine fibrosis contributes to gestational outcomes. Collagen deposition in the uterus is related to uterine aging. Senolytic therapies are an option for reducing health complications related to aging. We investigated effects of aging and the senolytic drug combination of dasatinib plus quercetin (D+Q) on uterine fibrosis. Forty mice, 20 young females (03-months) and 20 old females (18-months), were analyzed. Young (Y) and old (O) animals were divided into groups of 10 mice, with one treatment (T) group (YT and OT) and another control © group (YC and OC). Comparative analysis of and p53 gene expression and related microRNAs (miR34a, miR34b, miR34c, miR146a, miR449a, miR21a, miR126a, and miR181b) among groups was performed to test effects of age and treatment on collagen deposition pathways. Aging promoted downregulation of the signaling pathway ( = 0.005, = 0.031, and = 0.028, respectively) as well as a reduction in expression of miR34c ( = 0.029), miR126a ( = 0.009), and miR181b ( = 0.007). D+Q treatment increased p53 gene expression ( = 0.041) and decreased miR34a ( = 0.016). Our results demonstrate a role for the signaling pathway in uterine aging and suggest for the first time a possible anti-fibrotic effect in the uterus of D+Q senolytic therapy.
子宫纤维化会影响妊娠结局。子宫内的胶原蛋白沉积与子宫衰老有关。衰老细胞清除疗法是减少与衰老相关的健康并发症的一种选择。我们研究了衰老和衰老细胞清除药物组合达沙替尼加槲皮素（D+Q）对子宫纤维化的影响。分析了 40 只小鼠，其中 20 只为年轻雌性（03 个月），20 只为老年雌性（18 个月）。将年轻（Y）和老年（O）动物分为 10 只小鼠一组，每组分为治疗（T）组（YT 和 OT）和对照（C）组（YC 和 OC）。比较各组基因表达和相关 microRNAs（miR34a、miR34b、miR34c、miR146a、miR449a、miR21a、miR126a 和 miR181b），以测试年龄和治疗对胶原蛋白沉积途径的影响。衰老促进了信号通路的下调（分别为 = 0.005、= 0.031 和 = 0.028），以及 miR34c（= 0.029）、miR126a（= 0.009）和 miR181b（= 0.007）的表达减少。D+Q 治疗增加了 p53 基因的表达（= 0.041），降低了 miR34a（= 0.016）。我们的结果表明，信号通路在子宫衰老中起作用，并首次表明 D+Q 衰老细胞清除疗法可能对子宫具有抗纤维化作用。
